This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The Joint Center for Structural Genomics (JCSG) is a production center for the Protein Structure Initiative (PSI-2). The JCSG has developed a high-throughput structural platform that provides rapid structure determination by both x-ray crystallography and NMR on a range of targets from bacteria to human, and that includes challenging proteins, such as membrane proteins, eukaryotic proteins, and protein-protein complexes. Its goal is to constantly improve and update the pipeline through innovative technological advances, in order to both to increase the numbers of structures determined per year and reduce the cost per structure. A fundamental philosophy of JCSG is to export those developments to the general structural biology community so that they can benefit from any novel methodologies and technologies. The JCSG focuses on protein families that are most likely to contain novel folds or whose folds cannot be predicted by current methodologies. The biological and biomedical focus is on the "Central Machinery of Life" that constitutes those proteins conserved in the proteomes of all sequenced organisms. Subsets of these targets are likely to have important cellular roles implicated in disease. In summary, the overall JCSG goal is to provide a continuous flow of non-redundant, high-quality protein structures that, through judiciously chosen collaborations, will have a significant impact on the biological/biomedical sciences.